Finding one effective test for the three chest conditions that are the leading causes of death in China, without a high risk of false positives, would allow better control of the mortality rate by expanding opportunities for early treatment.
Researchers at three hospitals in China and one in the Netherlands are conducting the NELCIN B3 trial to explore low-dose CT as a “one-stop test” to identify early lung cancer, chronic obstructive pulmonary disease (COPD), and cardiovascular disease (CVD).
The study is testing whether measuring and treating nodules based on volume rather than diameter will reduce the rate of unnecessary referrals for lung cancer assessment, explained Li Fan, MD, of Shanghai Changzheng Hospital, during the May 7, 2021 program of the CT Screening Symposium.
A secondary objective is to adjust the cutoff values that signal the need for nodule follow up, and another is to identify risk factors for the “Big Three” diseases to determine who will benefit from screening.
“Building a high-risk model for the Chinese is very, very important,” Dr. Fan said, “because the Eastern [population] is very different from the Western, not only in culture but also in the medical environment.”
She reported strictly on the parameters and progress at her institution, the study’s leading hospital.
Rationale
The “heavy burden” of the Big Three is evidenced by their ranking by the World Health Organization (WHO) within the top 10 global causes of death in 2016. Heading the list that year was ischemic heart disease, which was associated with 9.5 million lost lives.
A 2018 study identified lung cancer as China’s most prevalent oncologic disease, tied to 10,422 diagnoses and 6,290 deaths per day. And although public awareness about COPD logs in at just 0.9% in China, the disease’s incidence rate there in residents aged 40 or older is 13.6%, with a mortality rate of 1.9 people per minute, Dr. Fan said.
She said that low-dose CT might better identify early COPD compared with the standard pulmonary function test, which does not pick up the initial changes associated with the condition.
Design
In 2018, Shanghai Changzheng Hospital launched its ongoing recruitment of 10,000 asymptomatic Shanghai residents aged 40 to 74 who have no history of lung cancer and are not pregnant. Participants are being randomly placed into either of two study arms.
Those in the intervention group receive 256-slice low-dose chest and sequential cardiac CT screening at baseline and a year later, with volume-based management of nodules modeled on protocols developed for the NELSON and ROBINSCA lung cancer screening trials. COPD management is according to the GOLD guideline, and medium- or high-risk CVD findings are referred to general practitioners.
Those in the control group receive 64-slice low-dose chest CT at baseline and a year later, with nodules managed according to standard practice—by diameter. While coronary artery calcium, emphysema, and/or bronchial wall thickness are qualitatively recorded, no management suggestions are given and general practitioners are not informed—also in line with standard practice.
Intervention group participants undergo physical exams before their first and second CT scans, providing information that could help identify Big Three risk factors.
In the fourth year after baseline, any diagnosis of lung cancer, COPD, or CVD, as well as related treatments, will be recorded for each participant and the outcomes of the study arms will be compared with regard to the frequency of unnecessary lung-nodule referrals and the detection of Big Three diseases. CT imaging biomarkers will be analyzed to determine the best cutoff values for early disease detection and to identify Big Three risk factors.
Results
Through December 1, 2020, Shanghai Changzheng Hospital had screened 3,439 residents and conducted three-month follow-ups in 161 and annual follow-ups in 1,511.
Fifty-four had received a cancer diagnosis, 38 of those confirmed pathologically. Now, artificial intelligence (AI) will compare the outcomes of the volume- and diameter-based protocols.
Also during that period, 2,018 CT emphysema evaluations revealed 512 cases, or an emphysema index of more than 6%. In addition, functional small airway disease was analyzed in 615 cases (Figure). CT for both of these purposes deserves further study, Dr. Fan said.
Finally, quantitative evaluation of coronary artery calcification has been conducted in 2,020 cases, revealing Agatston scores of 0 in 1,192 residents and higher values in the remaining participants. Eleven patients received stents based on these findings, she reported.
Overall, these results indicate that the “NELCIN B3 protocol is feasible and has great potential for Big Three screening,” Dr. Fan concluded.
She added that the one-stop test will allow hospitals to “build a database for deep data mining,” facilitating both AI research into the Big Three diseases and lung-nodule management strategy.
- 1. Computed Tomography Screening for Early Lung Cancer, COPD and Cardiovascular Disease in Shanghai: Rationale and Design of a Population based Comparative Study. Academic Radiology. 2020; S1076-6332(20)30048-30049.
